Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS
Phosphatidylserine (PS) in quiescent cells is predominantly confined to the inner leaflet of the plasma membrane. Externalization of PS is a marker of apoptosis, exocytosis, and some nonapoptotic activation events. It has been proposed that PS externalization is regulated by the activity of PLSCR1 (...
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Veröffentlicht in: | The Journal of biological chemistry 2008-04, Vol.283 (16), p.10904-10918 |
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description | Phosphatidylserine (PS) in quiescent cells is predominantly confined to the inner leaflet of the plasma membrane. Externalization of PS is a marker of apoptosis, exocytosis, and some nonapoptotic activation events. It has been proposed that PS externalization is regulated by the activity of PLSCR1 (phospholipid scramblase 1), a Ca²⁺-dependent endofacial plasma membrane protein, which is tyrosine-phosphorylated in activated cells. It is, however, unclear how the phosphorylation of PLSCR1 is related to its membrane topography, PS externalization, and exocytosis. Using rat basophilic leukemia cells as a model, we show that nonapoptotic PS externalization induced through the high affinity IgE receptor (FcεRI) or the glycosylphosphatidylinositol-anchored protein Thy-1 does not correlate with enhanced tyrosine phosphorylation of PLSCR1. In addition, PS externalization in FcεRI- or Thy-1-activated cells is not associated with alterations of PLSCR1 fine topography as detected by electron microscopy on isolated plasma membrane sheets. In contrast, activation by calcium ionophore A23187 induces changes in the cellular distribution of PLSCR1. We also show for the first time that in pervanadate-activated cells, exocytosis occurs even in the absence of PS externalization. Finally, we document here that tyrosine-phosphorylated PLSCR1 is preferentially located in detergent-insoluble membranes, suggesting its involvement in the formation of membrane-bound signaling assemblies. The combined data indicate that changes in the topography of PLSCR1 and its tyrosine phosphorylation, PS externalization, and exocytosis are independent phenomena that could be distinguished by employing specific conditions of activation. |
doi_str_mv | 10.1074/jbc.M710386200 |
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Externalization of PS is a marker of apoptosis, exocytosis, and some nonapoptotic activation events. It has been proposed that PS externalization is regulated by the activity of PLSCR1 (phospholipid scramblase 1), a Ca²⁺-dependent endofacial plasma membrane protein, which is tyrosine-phosphorylated in activated cells. It is, however, unclear how the phosphorylation of PLSCR1 is related to its membrane topography, PS externalization, and exocytosis. Using rat basophilic leukemia cells as a model, we show that nonapoptotic PS externalization induced through the high affinity IgE receptor (FcεRI) or the glycosylphosphatidylinositol-anchored protein Thy-1 does not correlate with enhanced tyrosine phosphorylation of PLSCR1. In addition, PS externalization in FcεRI- or Thy-1-activated cells is not associated with alterations of PLSCR1 fine topography as detected by electron microscopy on isolated plasma membrane sheets. In contrast, activation by calcium ionophore A23187 induces changes in the cellular distribution of PLSCR1. We also show for the first time that in pervanadate-activated cells, exocytosis occurs even in the absence of PS externalization. Finally, we document here that tyrosine-phosphorylated PLSCR1 is preferentially located in detergent-insoluble membranes, suggesting its involvement in the formation of membrane-bound signaling assemblies. The combined data indicate that changes in the topography of PLSCR1 and its tyrosine phosphorylation, PS externalization, and exocytosis are independent phenomena that could be distinguished by employing specific conditions of activation.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M710386200</identifier><identifier>PMID: 18281686</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Calcimycin - pharmacology ; Cell Line, Tumor ; Cell Membrane - metabolism ; Detergents - pharmacology ; Enzyme Inhibitors - pharmacology ; Exocytosis ; Ionophores - pharmacology ; Microscopy, Confocal ; Models, Biological ; Phosphatidylserines - chemistry ; Phospholipid Transfer Proteins - metabolism ; Phosphorylation ; Rats ; Tyrosine - chemistry ; Vanadates - pharmacology</subject><ispartof>The Journal of biological chemistry, 2008-04, Vol.283 (16), p.10904-10918</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18281686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smrž, Daniel</creatorcontrib><creatorcontrib>Lebduška, Pavel</creatorcontrib><creatorcontrib>Dráberová, L'ubica</creatorcontrib><creatorcontrib>Korb, Jan</creatorcontrib><creatorcontrib>Dráber, Petr</creatorcontrib><title>Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Phosphatidylserine (PS) in quiescent cells is predominantly confined to the inner leaflet of the plasma membrane. Externalization of PS is a marker of apoptosis, exocytosis, and some nonapoptotic activation events. It has been proposed that PS externalization is regulated by the activity of PLSCR1 (phospholipid scramblase 1), a Ca²⁺-dependent endofacial plasma membrane protein, which is tyrosine-phosphorylated in activated cells. It is, however, unclear how the phosphorylation of PLSCR1 is related to its membrane topography, PS externalization, and exocytosis. Using rat basophilic leukemia cells as a model, we show that nonapoptotic PS externalization induced through the high affinity IgE receptor (FcεRI) or the glycosylphosphatidylinositol-anchored protein Thy-1 does not correlate with enhanced tyrosine phosphorylation of PLSCR1. In addition, PS externalization in FcεRI- or Thy-1-activated cells is not associated with alterations of PLSCR1 fine topography as detected by electron microscopy on isolated plasma membrane sheets. In contrast, activation by calcium ionophore A23187 induces changes in the cellular distribution of PLSCR1. We also show for the first time that in pervanadate-activated cells, exocytosis occurs even in the absence of PS externalization. Finally, we document here that tyrosine-phosphorylated PLSCR1 is preferentially located in detergent-insoluble membranes, suggesting its involvement in the formation of membrane-bound signaling assemblies. The combined data indicate that changes in the topography of PLSCR1 and its tyrosine phosphorylation, PS externalization, and exocytosis are independent phenomena that could be distinguished by employing specific conditions of activation.</description><subject>Animals</subject><subject>Calcimycin - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Detergents - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Exocytosis</subject><subject>Ionophores - pharmacology</subject><subject>Microscopy, Confocal</subject><subject>Models, Biological</subject><subject>Phosphatidylserines - chemistry</subject><subject>Phospholipid Transfer Proteins - metabolism</subject><subject>Phosphorylation</subject><subject>Rats</subject><subject>Tyrosine - chemistry</subject><subject>Vanadates - pharmacology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kL1PwzAUxC0EgvKxMoInthQ_Ox82W9WmNFJoqqZIlCWyY6cEJU2JUyQG_ncitdzydKefTnqH0C2QIZDAffxU-fAlAMK4Twk5QQMgnDnMg7dTNCCEgiOoxy_QpbWfpJcr4BxdAKccfO4P0G-43ciNqc22w02BFx-N3X00VbkrNU7zVtaqktZgwOUWj_Ku_Jad0Xhsqso-4ehlEUfj0SpK5niaLPFilqSLWe8n6zgNl9E8xOHbKlzOR3H0fsBG80mfJeP1Kkmj9BqdFbKy5uZ4r9DrNFyNZ06cPPfFsVNQxjpHSq7zgHra1RxcP5CBZMbNFfeENkqowvOo77pKBQQIaOF7LCccgCshhA4Yu0IPh95d23ztje2yurR5_4TcmmZvs6DfRYBPe_DuCO5VbXS2a8tatj_Z_2A9cH8ACtlkctOWNntNKQFGCOfM8wX7A13ScZQ</recordid><startdate>20080418</startdate><enddate>20080418</enddate><creator>Smrž, Daniel</creator><creator>Lebduška, Pavel</creator><creator>Dráberová, L'ubica</creator><creator>Korb, Jan</creator><creator>Dráber, Petr</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20080418</creationdate><title>Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS</title><author>Smrž, Daniel ; Lebduška, Pavel ; Dráberová, L'ubica ; Korb, Jan ; Dráber, Petr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f233t-aa8dc725d4d81467a7a3e4cb859deb9bf552644bb70101d9653c08118b999d733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Calcimycin - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Detergents - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Exocytosis</topic><topic>Ionophores - pharmacology</topic><topic>Microscopy, Confocal</topic><topic>Models, Biological</topic><topic>Phosphatidylserines - chemistry</topic><topic>Phospholipid Transfer Proteins - metabolism</topic><topic>Phosphorylation</topic><topic>Rats</topic><topic>Tyrosine - chemistry</topic><topic>Vanadates - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smrž, Daniel</creatorcontrib><creatorcontrib>Lebduška, Pavel</creatorcontrib><creatorcontrib>Dráberová, L'ubica</creatorcontrib><creatorcontrib>Korb, Jan</creatorcontrib><creatorcontrib>Dráber, Petr</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smrž, Daniel</au><au>Lebduška, Pavel</au><au>Dráberová, L'ubica</au><au>Korb, Jan</au><au>Dráber, Petr</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2008-04-18</date><risdate>2008</risdate><volume>283</volume><issue>16</issue><spage>10904</spage><epage>10918</epage><pages>10904-10918</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Phosphatidylserine (PS) in quiescent cells is predominantly confined to the inner leaflet of the plasma membrane. Externalization of PS is a marker of apoptosis, exocytosis, and some nonapoptotic activation events. It has been proposed that PS externalization is regulated by the activity of PLSCR1 (phospholipid scramblase 1), a Ca²⁺-dependent endofacial plasma membrane protein, which is tyrosine-phosphorylated in activated cells. It is, however, unclear how the phosphorylation of PLSCR1 is related to its membrane topography, PS externalization, and exocytosis. Using rat basophilic leukemia cells as a model, we show that nonapoptotic PS externalization induced through the high affinity IgE receptor (FcεRI) or the glycosylphosphatidylinositol-anchored protein Thy-1 does not correlate with enhanced tyrosine phosphorylation of PLSCR1. In addition, PS externalization in FcεRI- or Thy-1-activated cells is not associated with alterations of PLSCR1 fine topography as detected by electron microscopy on isolated plasma membrane sheets. In contrast, activation by calcium ionophore A23187 induces changes in the cellular distribution of PLSCR1. We also show for the first time that in pervanadate-activated cells, exocytosis occurs even in the absence of PS externalization. Finally, we document here that tyrosine-phosphorylated PLSCR1 is preferentially located in detergent-insoluble membranes, suggesting its involvement in the formation of membrane-bound signaling assemblies. The combined data indicate that changes in the topography of PLSCR1 and its tyrosine phosphorylation, PS externalization, and exocytosis are independent phenomena that could be distinguished by employing specific conditions of activation.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>18281686</pmid><doi>10.1074/jbc.M710386200</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Calcimycin - pharmacology Cell Line, Tumor Cell Membrane - metabolism Detergents - pharmacology Enzyme Inhibitors - pharmacology Exocytosis Ionophores - pharmacology Microscopy, Confocal Models, Biological Phosphatidylserines - chemistry Phospholipid Transfer Proteins - metabolism Phosphorylation Rats Tyrosine - chemistry Vanadates - pharmacology |
title | Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS |
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